Africans have some of the highest rates of TB in the world, and it has long been suspected that genetic susceptibility plays a role. However, establishing candidate genes across populations to gauge risk has remained a challenge.

Now, a new study, published this week in the online Early Edition of the Proceedings of the National Academy of Sciences, found that a commonly occurring polymorphism in an immune response gene called macrophage migration inhibitory factor (MIF) confers almost a two-and-a-half fold increased risk for severe TB in patients from Uganda who were co-infected with HIV.

Low-expressers of MIF were almost twice as common among people of African ancestry as Caucasians.

“These results help explain the increased incidence of TB among this group,” said Rituparna Das, MD, PhD, an instructor in the division of Infectious Diseases at Penn Medicine. “Moreover, this is especially important in people co-infected with HIV, who have a compromised immune system and also constitute the major public health challenge of controlling TB.”

TB’s prevalence is rising because of drug resistance and an increasing number of patients who are co-infected with HIV. People with HIV and latent TB infection are at a much higher risk for progressing to active TB disease, so identifying patients earlier and getting them in preventative TB treatments is a priority.

“Therapies to augment MIF action are under development, and may provide a new tool to combat the global TB epidemic,” said Dr. Das.

Recently, Dr. Das received funding from the Penn Center for AIDS Research to further examine MIF in Botswana. The pilot project will examine the distribution of MIF genetic polymorphisms among HIV co-infected patients with pulmonary TB from the Botswana-UPenn Partnership site.

“With the high degree of TB exposure in that community, we hope to identify which patients are more likely to go on to develop active TB disease, and in the future, target these patients for preventive therapies,” said Dr. Das.

The research published in PNAS was supported by the National Institutes of Health and the Burrough Wellcome Fund. A release on the PNAS study can also be found here.

Other authors are Richard Bucala, Bae Hoon Kim, Jie Yao, Lin Leng, Rebecca Levy, Charles Murchison, and John MacMicking of Yale University; Mi-Sun Koo, Selvakumar Subbian, and Gilla Kaplan of the University of Medicine and Dentistry of New Jersey; Shevin Jacob of the University of Washington; William Burman of the University of Colorado; Christopher Moore of the University of Virginia; and John David of Harvard School of Public Health.

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